Functional analysis of Fanconi anemia genes that are involved in chromosomal stability and tumor prevention

• Project/Area Number: 17013083
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University (2007-2009); Hiroshima University (2006); Kawasaki Medical School (2005)
• Principal Investigator: TAKATA Minoru Kyoto University, 放射線生物研究センター, 教授 (30281728)
• Co-Investigator(Kenkyū-buntansha): 松下 暢子 川崎医科大学, 医学研究科, 助手 (30333222) ; 平野 世紀 川崎医科大学, 医学研究科, 助手 (20368616) ; 北尾 洋之 京都大学, 放射線生物研究センター, 研究員 (30368617) ; 冨田 純也 京都大学, 放射線生物研究センター, 研究員 (50511367)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥53,500,000 (Direct Cost: ¥53,500,000); Fiscal Year 2009: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2008: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2007: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2006: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2005: ¥10,700,000 (Direct Cost: ¥10,700,000)
• Keywords: ファンコニ貧血 / ゲノム不安定性 / FANCD2 / FANCI / ユビキチン化 / DNA修復 / シスプラチン / モノユビキチン化 / ゲノム安定性 / FAコア複合体 / DT40細胞 / 相同DNA組み換え

Research Abstract

Fanconi anemia is a hereditary disorder characterized by increased incidence of cancer and leukemia. FA is caused by a mutation in any one of the 14 FA genes. Their products form a nuclear biochemical network called FA pathway. We analyzed molecular function of the FA pathway by making knockout mutant cell line from chicken DT40 cells. We have partially clarified molecular details of the FA pathway and its regulatory mechanism in the DNA damage response.

Research Products

• [Journal Article] Chemopreventive effects of gefitinib on nonsmoking-related lung tumorigenesis in activating epidermal growth factor receptor transgenic mice. (2009)
  • Author(s): Ohashi K., Takigawa N., Osawa M., Ichihara E., Takeda H., Kubo T., Hirano S., Yoshino T., Takata M., animoto M., Kiura K.
  • Journal Title: Cancer Res. 69 Pages: 7088-7095
  • Peer Reviewed
• [Journal Article] TheFanconi anemia pathway: Insights from somatic cell genetics using DT40 cell line. (2009)
  • Author(s): Takata M., Ishiai M., Kitao H.
  • Journal Title: Invited review. Mutat. Res. 668 Pages: 92-102
  • Peer Reviewed
• [Journal Article] The Fanconi anemia pathway : Insights from somatic cell genetics using DT40 cell line. (2009)
  • Author(s): Takata M, Ishiai M, Kitao H
  • Journal Title: Mutat Res 668 Pages: 92-102
  • Peer Reviewed
• [Journal Article] Chemopreventive effects of gefitinib on nonsmoking-related lung tumori genesis in activating epidermal growth factor receptor transgenic mice (2009)
  • Author(s): Ohashi K, Takigawa N, Osawa M, Ichihara E, Takeda H, Kubo T, Hirano S, Yoshino T, Takata M, Tanimoto M, Kiura K.
  • Journal Title: Can Res 69 Pages: 7088-7095
  • Peer Reviewed
• [Journal Article] Insights from somatic cell genetics using DT40 cellline. Invited review (2009)
  • Author(s): Takata M, Ishiai M, Kitao H., et.al.
  • Journal Title: Mutation Research Fanconi anemia Special Issue(in press)
  • Peer Reviewed
• [Journal Article] FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway. (2008)
  • Author(s): Ishiai M., Kitao H., Smogorzewska A., Tomida J., Kinomura A., Uchida E., Saberi A., Kinoshita E., Kinoshita-Kikuta E., Koike T., Tashiro S., Elledge S.J., Takata M.
  • Journal Title: Nat. Struc. Mol. Biol. 15 Pages: 1138-1146
  • Peer Reviewed
• [Journal Article] Detection of phosphorylation on large proteins by western blotting using Phos-tag containing gel. (2008)
  • Author(s): Tomida J., Kitao H., Kinoshita E., Takata., M.
  • Journal Title: Nature Protocols 232
  • Peer Reviewed
• [Journal Article] FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2, XRCC3. (2008)
  • Author(s): Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E., Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J.
  • Journal Title: Oncogene 27 Pages: 3641-3652
  • Peer Reviewed
• [Journal Article] Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion. (2008)
  • Author(s): Kitao H., Kimura M., Yamamoto K., Seo H., Namikoshi K., Agata Y., Ohta K., Takata M.
  • Journal Title: Int. Immunol. 20 Pages: 277-284
  • NAID: 10021239538
  • Peer Reviewed
• [Journal Article] KU70/80, DNA-PKcs, and Artemis are essential for the rapidinduction of apoptosis after massive DSB formation (2008)
  • Author(s): Abe T, Ishiai M, Hosono Y, Yoshimura A, Tada S, et.al.
  • Journal Title: Cell Signal 20 Pages: 1978-1985
  • Peer Reviewed
• [Journal Article] FANCI phosphorylation functions as a molecular switchto turn on the Fanconi anemia pathway (2008)
  • Author(s): Ishiai Kitao H, Smogorzewska A, Tomida J, Kinomura A, et.al.
  • Journal Title: Nat Struct Mol Biol 15 Pages: 1138-1146
  • Peer Reviewed
• [Journal Article] Enhancement of radiation induced cell death in chicken Blymphocytes by withaferin A (2008)
  • Author(s): Uma Devi P, Utsumiz H, Takata M, Takeda S., et.al.
  • Journal Title: Indian J Exp Biol 46 Pages: 437-442
  • Peer Reviewed
• [Journal Article] Current topics in DNA double-strand break repair. (2008)
  • Author(s): Kobayashi J, et. al.
  • Journal Title: J Radiat Res (Tokyo) 49 Pages: 93-103
  • Peer Reviewed
• [Journal Article] FANCG promotes formation of a newly identified protein complexcontaining BRCA2, FANCD2 and XRCC3. (2008)
  • Author(s): Wilson JB, et. al.
  • Journal Title: Oncogene (epub ahead of print)
  • Peer Reviewed
• [Journal Article] Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion. (2008)
  • Author(s): Kitao H, et. al.
  • Journal Title: Int Immunology 20 Pages: 277-84
  • Peer Reviewed
• [Journal Article] Deubiquitination of FANCD2 Is Required for DNA Crosslink Repair. (2007)
  • Author(s): Oestergaard V.H., Langevin F., Kuiken H.J., Pace P., Niedzwiedz W., Simpson L.J., Ohzeki M., Takata M., Sale J.E., Patel K.J.
  • Journal Title: Mol. Cell 28 Pages: 798-809
  • Peer Reviewed
• [Journal Article] in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde. (2007)
  • Author(s): Ridpath J.R., Nakamura A., Tano K., Luke A.M., Sonoda E., Arakawa H., Buerstedde J.M., Gillespie D.A., Sale J.E., Yamazoe M., Bishop D.K., Takata M., Takeda S., Watanabe M., Swenberg J.A., Nakamura J. Cells deficient
  • Journal Title: Cancer Res. 67 Pages: 11117-11122
  • Peer Reviewed
• [Journal Article] FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway. (2007)
  • Author(s): Ling C., Ishiai M., Ali A.M., Medhurst A.L., Neveling K., Kalb R., Yan Z., Xue Y., Oostra A.B., Auerbach A.D., Hoatlin M.E., Schindler D., Joenje H., de Winter J.P., Takata M., Meetei A.R., Wang W.
  • Journal Title: EMBO J. 26 Pages: 2104-2114
  • Peer Reviewed
• [Journal Article] genetic analysis of a human disease using chicken system. (2007)
  • Author(s): Takata M, Kitao H, Ishiai M. Fanconianemia
  • Journal Title: Cytogenet Genome Res. 117 Pages: 346-351
  • Peer Reviewed
• [Journal Article] Emergence of Epidermal Growth Factor Receptor T790M Mutation during Chronic Exposure to Gefitinib in a Non Small Cell Lung Cancer Cell Line. (2007)
  • Author(s): Ogino A., Kitao H., A., Ishiai M., Kozuki T., Takigawa N., Hirano S., Uchida Takata M., Kiura K., Tanimoto M.
  • Journal Title: Cancer Res. 67 Pages: 7807-7014
  • Peer Reviewed
• [Journal Article] A requirement of FancL and FancD2 monoubiquitination in DNA repair. (2007)
  • Author(s): Seki S., Ohzeki M., Uchida A., Hirano S., Matsushita N., Kitao H., Oda T., Yamashita T., Kashihara N., Tsubahara A., Takata M., Ishiai M.
  • Journal Title: Genes Cells 12 Pages: 299-310
  • Peer Reviewed
• [Journal Article] Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and nroteotoxic stress. (2007)
  • Author(s): Messaoudi L, et. al.
  • Journal Title: Nucleic Acids Res 35 Pages: 6571-6587
  • Peer Reviewed
• [Journal Article] Deubiquitination of FANCD2 Is Required for DNA Crosslink Repair. (2007)
  • Author(s): Oestergaard VH, et. al.
  • Journal Title: Mol Cell 28 Pages: 798-809
  • Peer Reviewed
• [Journal Article] Cells deficient in the FANC/BRCA pathway are hypersensitive toplasma levels of formaldehyde. (2007)
  • Author(s): Ridpath JR, et. al.
  • Journal Title: Cancer Res 67 Pages: 11117-22
  • Peer Reviewed
• [Journal Article] A requirement of FancL and FancD2 monoubiquitination in DNA repair. (2007)
  • Author(s): Seki S, Ohzeki M, et al.
  • Journal Title: Genes Cells 12・3 Pages: 299-310
• [Journal Article] Characterization of the short isoform of Helios overexpressed in patients with T-cell malignancies. (2007)
  • Author(s): Tabayashi T, Ishimaru F, Takata M, et al.
  • Journal Title: Cancer science 98・2 Pages: 182-188
• [Journal Article] Activation of downstream epidermal growth factor receptor (EGFR) signaling provides gefitinib-resistance in cells carrving EGFR mutation. (2007)
  • Author(s): Uchida A, Hirano S, et al.
  • Journal Title: Cancer science 98・3 Pages: 357-363
• [Journal Article] Functional interplay between BRCA2/FANCD1 and FANCC in DNA repair. (2006)
  • Author(s): Kitao H., Yamamoto K., Matsushita N., Ohzeki M., Ishiai M., Takata M.
  • Journal Title: J. Biol. Chem. 281 Pages: 21312-21320
  • Peer Reviewed
• [Journal Article] Functional interplay between BRCA2/FANCDI and FANCC in DNA repair. (2006)
  • Author(s): Kitao H, Yamanioto K. et al.
  • Journal Title: Journal of Biological Chemistry 281・302 Pages: 21312-21320
• [Journal Article] 53BP1 contributes to survival of cells irradiated with x-ray during G1 without Ku70 or Artemis. (2006)
  • Author(s): Iwabuchi K, Hashimoto M, et al.
  • Journal Title: Genes Cells. 11・8 Pages: 935-948
• [Journal Article] A FancD2-Monoubiquitin Fusion Reveals Hidden Functions of Fanconi Anemia Core Complex in DNA Repair. (2005)
  • Author(s): Matsushita N., Kitao H., Ishiai M., Nagashima N., Hirano S., Okawa K., Ohta T., Yu D.S., McHugh P.J., Hickson I.D., Venkitaraman A.R., Kurumizaka H., Takata M.
  • Journal Title: Mol. Cell 19 Pages: 841-847
  • Peer Reviewed
• [Journal Article] Role of NAD-dependent deacetylases SIRT1 and SIRT2 in radiation-and cisplatin-induced cell death in vertebrate cells. (2005)
  • Author(s): Nobuko Matsushita, et al.
  • Journal Title: Genes Cells 10(4) Pages: 321-332
• [Journal Article] FancD2-Monoubiquitin Fusion Reveals Hidden Functions of Fanconi Anemia Core Complex in DNA Repair. (2005)
  • Author(s): Matsushita N., et al.
  • Journal Title: Mol Cell 16;19(6) Pages: 841-847
• [Journal Article] Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells. (2005)
  • Author(s): Nojima K., et al.
  • Journal Title: Cancer Res. 15;65(24) Pages: 11704-11711
• [Journal Article] FAAPIOO is essential for activation of the Fanconi anemia-associated DNA damage response pathway.
  • Author(s): Chen Ling, Masamichi Ishiai, et al.
  • Journal Title: The EMBO Journal (in press)
• [Presentation] Regulation Of Cross-Link Repair Through The Fanconi Anemia Pathway. (2009)
  • Author(s): Takata M., Tomida J., Itaya A., Shigechi T., Ishiai M.
  • Organizer: 高松宮がん研究基金シンポジウム
  • Place of Presentation: 東京
• [Presentation] 高発がん遺伝病ファンコニ貧血の分子メカニズム, 小児血液腫瘍の発症リスクと先天異常 (2009)
  • Author(s): 高田穣
  • Organizer: 第71回日本血液学会学術集会シンポジウム
  • Place of Presentation: 京都
• [Presentation] DNA damage response and hematological disorder, DNA damage signaling in the Fanconi anemia pathogenesis (2009)
  • Author(s): Takata M.
  • Organizer: 第51回小児血液学会シンポジウム
  • Place of Presentation: 千葉
• [Presentation] A novel role of the FA core complex in FANCI phosphorylation, an important switch in the FA pathway. (2009)
  • Author(s): Minoru Takata, Junya Tomida, Tomoko Shigechi, Hiroyuki Kitao, Akiko Itaya, Masamichilshiai
  • Organizer: Twenty-first Annual Fanconi Anemia Research Fund Scientific Symposium
  • Place of Presentation: Baltimore, MA, USA
• [Presentation] REGULATION OF CROSS-LINK REPAIR THROUGH THE FANCONI ANEMIA PATHWAY. (2009)
  • Author(s): Minoru Takata, Junya Tomida, Akiko Itaya, Tomoko Shigechi, Masamichi Ishiai
  • Organizer: The Fortieth International Symposium of the Princess Takamatsu Cancer Research Fund
  • Place of Presentation: Tokyo
• [Presentation] 高発がん遺伝病ファンコニ貧血の分子メカニズム (2009)
  • Author(s): 高田穣
  • Organizer: 第71回日本血液学会学術集会シンポジウム「小児血液腫瘍の発症リスクと先天異常」
  • Place of Presentation: 京都市国際会館
• [Presentation] DNA damage signaling in the Fanconi anemia pathogenesis (2009)
  • Author(s): Minoru Takata
  • Organizer: 第51回小児血液学会血液プレジデンシャルシンポジウム「DNA damage response and hematological disorder」
  • Place of Presentation: 千葉東京ベイホテル東急
• [Presentation] ファンコニ貧血経路によるゲノム安定化メカニズム (2008)
  • Author(s): 高由穣
  • Organizer: 第3回放射線防護研究センターシンポジウム
  • Place of Presentation: 千葉県放射線総合医学研究所
  • Year and Date: 2008-12-16
• [Presentation] FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway. Symposium "DNA repair network deficiency and carcinogenesis". (2008)
  • Author(s): Ishiai M., Kitao H., Takata M.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] ゲノムの安定性維持メカニズムとファンコニ貧血 (2008)
  • Author(s): 高田穣
  • Organizer: 第1 0 1回小児血液腫瘍懇話会
  • Place of Presentation: 東京・経団連会館
  • Year and Date: 2008-07-18
• [Presentation] FANCI phosphorylation functions as a-molecular switch toturn on the Fanconi anemia pathway. Symposium (2008)
  • Author(s): Ishiai M, Kitao H, Takata M
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] Role of Fanci protein and its phosphorylation for the Fanconiaanemia pathway function (2007)
  • Author(s): Minoru Takata
  • Organizer: Nineteenth Annual Fanconia Anemia Research Fund Sceintific Symposium
  • Place of Presentation: The Westin Michigan Avenue, Chicago,II, USA
  • Year and Date: 2007-10-10
• [Presentation] Chromosome and Genome Stability and FancD2/FancI complex regulates crosslink repair in the Fanconi anemia pathway. Instability (2007)
  • Author(s): Takata M.
  • Organizer: Chromosome Cycle International Symposium
  • Place of Presentation: 大阪
• [Presentation] Functional Pathways in Recombinational Repair. (2007)
  • Author(s): Takata M.
  • Organizer: Keystone Symposia "Genome Instability and Repair" Breckenridge
  • Place of Presentation: CO, USA.
• [Book] Fanconi anemia. A paradigmatic disease for the understanding of cancer and aging. (2007)
  • Author(s): Nanda I, et. al.
  • Total Pages: 229
  • Publisher: Karger, Switzerland
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